<?xml version="1.0" encoding="us-ascii"?>
<!-- Created by Merrill Corporation -->
<!--XBRL document created with Toppan Merrill Bridge  9.1.0.83 -->
<!--Based on XBRL 2.1-->
<!--Created on: 5/7/2019 1:14:19 PM-->
<!--Modified on: 5/7/2019 1:14:19 PM-->
<link:linkbase xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd" xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xbrli="http://www.xbrl.org/2003/instance">
  <roleRef xlink:type="simple" xlink:href="mdgl-20190331.xsd#StatementCondensedConsolidatedBalanceSheets" roleURI="http://www.madrigalpharma.com/role/StatementCondensedConsolidatedBalanceSheets" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="mdgl-20190331.xsd#StatementCondensedConsolidatedStatementsOfOperations" roleURI="http://www.madrigalpharma.com/role/StatementCondensedConsolidatedStatementsOfOperations" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="mdgl-20190331.xsd#StatementCondensedConsolidatedStatementsOfComprehensiveLoss" roleURI="http://www.madrigalpharma.com/role/StatementCondensedConsolidatedStatementsOfComprehensiveLoss" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="mdgl-20190331.xsd#StatementCondensedConsolidatedStatementsOfCashFlows" roleURI="http://www.madrigalpharma.com/role/StatementCondensedConsolidatedStatementsOfCashFlows" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="mdgl-20190331.xsd#DisclosureCashCashEquivalentsAndMarketableSecuritiesDetails" roleURI="http://www.madrigalpharma.com/role/DisclosureCashCashEquivalentsAndMarketableSecuritiesDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="mdgl-20190331.xsd#DisclosureLeasesDetails" roleURI="http://www.madrigalpharma.com/role/DisclosureLeasesDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="mdgl-20190331.xsd#DisclosureLeasesDetailsCalc2" roleURI="http://www.madrigalpharma.com/role/DisclosureLeasesDetailsCalc2" xmlns="http://www.xbrl.org/2003/linkbase" />
  <calculationLink xlink:role="http://www.madrigalpharma.com/role/StatementCondensedConsolidatedBalanceSheets" xlink:type="extended" xlink:title="00100 - Statement - Condensed Consolidated Balance Sheets" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_Assets" xlink:label="us-gaap_Assets" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_AssetsCurrent" xlink:label="us-gaap_AssetsCurrent_636928316581892625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Assets" xlink:to="us-gaap_AssetsCurrent_636928316581892625" order="1" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_CashAndCashEquivalentsAtCarryingValue" xlink:label="us-gaap_CashAndCashEquivalentsAtCarryingValue_636928316581892625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent_636928316581892625" xlink:to="us-gaap_CashAndCashEquivalentsAtCarryingValue_636928316581892625" order="1" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent_636928316581892625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent_636928316581892625" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent_636928316581892625" order="2" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_PrepaidExpenseAndOtherAssetsCurrent" xlink:label="us-gaap_PrepaidExpenseAndOtherAssetsCurrent_636928316581892625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent_636928316581892625" xlink:to="us-gaap_PrepaidExpenseAndOtherAssetsCurrent_636928316581892625" order="3" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_PropertyPlantAndEquipmentNet" xlink:label="us-gaap_PropertyPlantAndEquipmentNet_636928316581892625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Assets" xlink:to="us-gaap_PropertyPlantAndEquipmentNet_636928316581892625" order="2" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_OperatingLeaseRightOfUseAsset" xlink:label="us-gaap_OperatingLeaseRightOfUseAsset_636928316581892625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Assets" xlink:to="us-gaap_OperatingLeaseRightOfUseAsset_636928316581892625" order="3" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_LiabilitiesAndStockholdersEquity" xlink:label="us-gaap_LiabilitiesAndStockholdersEquity_635435209156581690" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_Liabilities" xlink:label="us-gaap_Liabilities_636928316581892625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesAndStockholdersEquity_635435209156581690" xlink:to="us-gaap_Liabilities_636928316581892625" order="1" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_LiabilitiesCurrent" xlink:label="us-gaap_LiabilitiesCurrent_636928316581892625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Liabilities_636928316581892625" xlink:to="us-gaap_LiabilitiesCurrent_636928316581892625" order="1" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_AccountsPayableCurrent" xlink:label="us-gaap_AccountsPayableCurrent_636928316581892625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesCurrent_636928316581892625" xlink:to="us-gaap_AccountsPayableCurrent_636928316581892625" order="1" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_AccruedLiabilitiesCurrent" xlink:label="us-gaap_AccruedLiabilitiesCurrent_636928316581892625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesCurrent_636928316581892625" xlink:to="us-gaap_AccruedLiabilitiesCurrent_636928316581892625" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_OperatingLeaseLiabilityCurrent" xlink:label="us-gaap_OperatingLeaseLiabilityCurrent_636928316581892625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesCurrent_636928316581892625" xlink:to="us-gaap_OperatingLeaseLiabilityCurrent_636928316581892625" order="3" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_LiabilitiesNoncurrent" xlink:label="us-gaap_LiabilitiesNoncurrent_636928316581892625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Liabilities_636928316581892625" xlink:to="us-gaap_LiabilitiesNoncurrent_636928316581892625" order="2" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_OperatingLeaseLiabilityNoncurrent" xlink:label="us-gaap_OperatingLeaseLiabilityNoncurrent_636928316581892625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesNoncurrent_636928316581892625" xlink:to="us-gaap_OperatingLeaseLiabilityNoncurrent_636928316581892625" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_StockholdersEquity" xlink:label="us-gaap_StockholdersEquity_636928316581902625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesAndStockholdersEquity_635435209156581690" xlink:to="us-gaap_StockholdersEquity_636928316581902625" order="2" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_PreferredStockValue" xlink:label="us-gaap_PreferredStockValue_636928316581902625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_StockholdersEquity_636928316581902625" xlink:to="us-gaap_PreferredStockValue_636928316581902625" order="1" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_CommonStockValue" xlink:label="us-gaap_CommonStockValue_636928316581902625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_StockholdersEquity_636928316581902625" xlink:to="us-gaap_CommonStockValue_636928316581902625" order="2" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_AdditionalPaidInCapitalCommonStock" xlink:label="us-gaap_AdditionalPaidInCapitalCommonStock_636928316581902625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_StockholdersEquity_636928316581902625" xlink:to="us-gaap_AdditionalPaidInCapitalCommonStock_636928316581902625" order="3" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax" xlink:label="us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax_636928316581902625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_StockholdersEquity_636928316581902625" xlink:to="us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax_636928316581902625" order="4" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_RetainedEarningsAccumulatedDeficit" xlink:label="us-gaap_RetainedEarningsAccumulatedDeficit_636928316581902625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_StockholdersEquity_636928316581902625" xlink:to="us-gaap_RetainedEarningsAccumulatedDeficit_636928316581902625" order="5" use="optional" weight="1" />
  </calculationLink>
  <calculationLink xlink:role="http://www.madrigalpharma.com/role/StatementCondensedConsolidatedStatementsOfOperations" xlink:type="extended" xlink:title="00200 - Statement - Condensed Consolidated Statements of Operations" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_NetIncomeLoss" xlink:label="us-gaap_NetIncomeLoss" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_OperatingIncomeLoss" xlink:label="us-gaap_OperatingIncomeLoss_636928316581902625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetIncomeLoss" xlink:to="us-gaap_OperatingIncomeLoss_636928316581902625" order="1" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_OperatingExpenses" xlink:label="us-gaap_OperatingExpenses_636928316581902625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_OperatingIncomeLoss_636928316581902625" xlink:to="us-gaap_OperatingExpenses_636928316581902625" order="1" use="optional" weight="-1" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ResearchAndDevelopmentExpenseExcludingAcquiredInProcessCost" xlink:label="us-gaap_ResearchAndDevelopmentExpenseExcludingAcquiredInProcessCost_636928316581902625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_OperatingExpenses_636928316581902625" xlink:to="us-gaap_ResearchAndDevelopmentExpenseExcludingAcquiredInProcessCost_636928316581902625" order="1" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_GeneralAndAdministrativeExpense" xlink:label="us-gaap_GeneralAndAdministrativeExpense_636928316581902625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_OperatingExpenses_636928316581902625" xlink:to="us-gaap_GeneralAndAdministrativeExpense_636928316581902625" order="2" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_InterestIncomeOther" xlink:label="us-gaap_InterestIncomeOther_636928316581902625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetIncomeLoss" xlink:to="us-gaap_InterestIncomeOther_636928316581902625" order="2" use="optional" weight="1" priority="2" />
  </calculationLink>
  <calculationLink xlink:role="http://www.madrigalpharma.com/role/StatementCondensedConsolidatedStatementsOfComprehensiveLoss" xlink:type="extended" xlink:title="00300 - Statement - Condensed Consolidated Statements of Comprehensive Loss" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ComprehensiveIncomeNetOfTax" xlink:label="us-gaap_ComprehensiveIncomeNetOfTax_635435210967172731" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_NetIncomeLoss" xlink:label="us-gaap_NetIncomeLoss_636928316581902625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_ComprehensiveIncomeNetOfTax_635435210967172731" xlink:to="us-gaap_NetIncomeLoss_636928316581902625" order="1" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" xlink:label="us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent_636928316581902625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_ComprehensiveIncomeNetOfTax_635435210967172731" xlink:to="us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent_636928316581902625" order="2" use="optional" weight="1" />
  </calculationLink>
  <calculationLink xlink:role="http://www.madrigalpharma.com/role/StatementCondensedConsolidatedStatementsOfCashFlows" xlink:type="extended" xlink:title="00500 - Statement - Condensed Consolidated Statements of Cash Flows" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect" xlink:label="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:label="us-gaap_NetCashProvidedByUsedInOperatingActivities_636928316581912625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect" xlink:to="us-gaap_NetCashProvidedByUsedInOperatingActivities_636928316581912625" order="1" use="optional" weight="1" priority="1" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ProfitLoss" xlink:label="us-gaap_ProfitLoss_636928316581912625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_636928316581912625" xlink:to="us-gaap_ProfitLoss_636928316581912625" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ShareBasedCompensation" xlink:label="us-gaap_ShareBasedCompensation_636928316581912625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_636928316581912625" xlink:to="us-gaap_ShareBasedCompensation_636928316581912625" order="2" use="optional" weight="1" priority="1" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_DepreciationDepletionAndAmortization" xlink:label="us-gaap_DepreciationDepletionAndAmortization_636928316581912625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_636928316581912625" xlink:to="us-gaap_DepreciationDepletionAndAmortization_636928316581912625" order="3" use="optional" weight="1" priority="1" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets" xlink:label="us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets_636928316581912625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_636928316581912625" xlink:to="us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets_636928316581912625" order="4" use="optional" weight="-1" priority="1" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_IncreaseDecreaseInAccountsPayableTrade" xlink:label="us-gaap_IncreaseDecreaseInAccountsPayableTrade_636928316581912625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_636928316581912625" xlink:to="us-gaap_IncreaseDecreaseInAccountsPayableTrade_636928316581912625" order="5" use="optional" weight="1" priority="1" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_IncreaseDecreaseInAccruedLiabilities" xlink:label="us-gaap_IncreaseDecreaseInAccruedLiabilities_636928316581912625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_636928316581912625" xlink:to="us-gaap_IncreaseDecreaseInAccruedLiabilities_636928316581912625" order="6" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="mdgl-20190331.xsd#mdgl_IncreaseDecreaseInAccruedInterestNetOfInterestReceived" xlink:label="mdgl_IncreaseDecreaseInAccruedInterestNetOfInterestReceived_636928316581912625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_636928316581912625" xlink:to="mdgl_IncreaseDecreaseInAccruedInterestNetOfInterestReceived_636928316581912625" order="7" use="optional" weight="1" priority="1" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivities" xlink:label="us-gaap_NetCashProvidedByUsedInInvestingActivities_636928316581912625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect" xlink:to="us-gaap_NetCashProvidedByUsedInInvestingActivities_636928316581912625" order="2" use="optional" weight="1" priority="1" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_PaymentsToAcquireMarketableSecurities" xlink:label="us-gaap_PaymentsToAcquireMarketableSecurities_636928316581912625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInInvestingActivities_636928316581912625" xlink:to="us-gaap_PaymentsToAcquireMarketableSecurities_636928316581912625" order="1" use="optional" weight="-1" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_ProceedsFromMaturitiesPrepaymentsAndCallsOfAvailableForSaleSecurities" xlink:label="us-gaap_ProceedsFromMaturitiesPrepaymentsAndCallsOfAvailableForSaleSecurities_636928316581912625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInInvestingActivities_636928316581912625" xlink:to="us-gaap_ProceedsFromMaturitiesPrepaymentsAndCallsOfAvailableForSaleSecurities_636928316581912625" order="2" use="optional" weight="1" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_PaymentsToAcquirePropertyPlantAndEquipment" xlink:label="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_636928316581912625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInInvestingActivities_636928316581912625" xlink:to="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_636928316581912625" order="3" use="optional" weight="-1" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivities" xlink:label="us-gaap_NetCashProvidedByUsedInFinancingActivities_636928316581912625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect" xlink:to="us-gaap_NetCashProvidedByUsedInFinancingActivities_636928316581912625" order="3" use="optional" weight="1" priority="1" />
    <loc xlink:type="locator" xlink:href="mdgl-20190331.xsd#mdgl_ProceedsFromIssuanceOfCommonStockIncludingExerciseOfCommonStockOptions" xlink:label="mdgl_ProceedsFromIssuanceOfCommonStockIncludingExerciseOfCommonStockOptions_636928316581912625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInFinancingActivities_636928316581912625" xlink:to="mdgl_ProceedsFromIssuanceOfCommonStockIncludingExerciseOfCommonStockOptions_636928316581912625" order="1" use="optional" weight="1" priority="2" />
  </calculationLink>
  <calculationLink xlink:role="http://www.madrigalpharma.com/role/DisclosureCashCashEquivalentsAndMarketableSecuritiesDetails" xlink:type="extended" xlink:title="40401 - Disclosure - Cash, Cash Equivalents and Marketable Securities (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="mdgl-20190331.xsd#mdgl_CashCashEquivalentsAndShortTermInvestmentsAtCost" xlink:label="mdgl_CashCashEquivalentsAndShortTermInvestmentsAtCost" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_CashCashEquivalentsAndShortTermInvestments" xlink:label="us-gaap_CashCashEquivalentsAndShortTermInvestments_636928316581912625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="mdgl_CashCashEquivalentsAndShortTermInvestmentsAtCost" xlink:to="us-gaap_CashCashEquivalentsAndShortTermInvestments_636928316581912625" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="mdgl-20190331.xsd#mdgl_CashAndCashEquivalentsAndAvailableForSaleSecuritiesGrossUnrealizedGains" xlink:label="mdgl_CashAndCashEquivalentsAndAvailableForSaleSecuritiesGrossUnrealizedGains_636928316581912625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="mdgl_CashCashEquivalentsAndShortTermInvestmentsAtCost" xlink:to="mdgl_CashAndCashEquivalentsAndAvailableForSaleSecuritiesGrossUnrealizedGains_636928316581912625" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="mdgl-20190331.xsd#mdgl_CashAndCashEquivalentsAndAvailableForSaleSecuritiesGrossUnrealizedLosses" xlink:label="mdgl_CashAndCashEquivalentsAndAvailableForSaleSecuritiesGrossUnrealizedLosses_636928316581922625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="mdgl_CashCashEquivalentsAndShortTermInvestmentsAtCost" xlink:to="mdgl_CashAndCashEquivalentsAndAvailableForSaleSecuritiesGrossUnrealizedLosses_636928316581922625" order="3" use="optional" weight="-1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:label="us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtSecurities_636928316581922625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtSecurities_636928316581922625" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" xlink:label="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_636928316581922625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:to="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_636928316581922625" order="2" use="optional" weight="-1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" xlink:label="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_636928316581922625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:to="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_636928316581922625" order="3" use="optional" weight="1" priority="2" />
  </calculationLink>
  <calculationLink xlink:role="http://www.madrigalpharma.com/role/DisclosureLeasesDetails" xlink:type="extended" xlink:title="40701 - Disclosure - Leases (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_OperatingLeasesFutureMinimumPaymentsDue" xlink:label="us-gaap_OperatingLeasesFutureMinimumPaymentsDue" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_OperatingLeasesFutureMinimumPaymentsRemainderOfFiscalYear" xlink:label="us-gaap_OperatingLeasesFutureMinimumPaymentsRemainderOfFiscalYear_636928316581922625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_OperatingLeasesFutureMinimumPaymentsDue" xlink:to="us-gaap_OperatingLeasesFutureMinimumPaymentsRemainderOfFiscalYear_636928316581922625" order="1" use="optional" weight="1" priority="3" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_OperatingLeasesFutureMinimumPaymentsDueInTwoYears" xlink:label="us-gaap_OperatingLeasesFutureMinimumPaymentsDueInTwoYears_636928316581922625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_OperatingLeasesFutureMinimumPaymentsDue" xlink:to="us-gaap_OperatingLeasesFutureMinimumPaymentsDueInTwoYears_636928316581922625" order="2" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_OperatingLeasesFutureMinimumPaymentsDueInThreeYears" xlink:label="us-gaap_OperatingLeasesFutureMinimumPaymentsDueInThreeYears_636928316581922625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_OperatingLeasesFutureMinimumPaymentsDue" xlink:to="us-gaap_OperatingLeasesFutureMinimumPaymentsDueInThreeYears_636928316581922625" order="3" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_OperatingLeasesFutureMinimumPaymentsDueInFourYears" xlink:label="us-gaap_OperatingLeasesFutureMinimumPaymentsDueInFourYears_636928316581922625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_OperatingLeasesFutureMinimumPaymentsDue" xlink:to="us-gaap_OperatingLeasesFutureMinimumPaymentsDueInFourYears_636928316581922625" order="4" use="optional" weight="1" priority="2" />
  </calculationLink>
  <calculationLink xlink:role="http://www.madrigalpharma.com/role/DisclosureLeasesDetailsCalc2" xlink:type="extended" xlink:title="40701 - Disclosure - Leases (Details) - calc 2" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_OperatingLeasesFutureMinimumPaymentsDue" xlink:label="us-gaap_OperatingLeasesFutureMinimumPaymentsDue" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_OperatingLeaseLiability" xlink:label="us-gaap_OperatingLeaseLiability_636928316581922625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_OperatingLeasesFutureMinimumPaymentsDue" xlink:to="us-gaap_OperatingLeaseLiability_636928316581922625" order="1" use="optional" weight="1" priority="2" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount_636928316581922625" />
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_OperatingLeasesFutureMinimumPaymentsDue" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount_636928316581922625" order="2" use="optional" weight="1" priority="2" />
  </calculationLink>
</link:linkbase>
